TRPV1 enhances the afferent response to P2X receptor activation in the mouse urinary bladder

Abstract Both TRPV1 and P2X receptors present on bladder sensory nerve fibres have been implicated in mechanosensation during bladder filling. The aim of this study was to determine possible interactions between these receptors in modulating afferent nerve activity. In wildtype (TRPV1+/+) and TRPV1...

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Autores principales:	Luke Grundy, Donna M. Daly, Christopher Chapple, David Grundy, Russ Chess-Williams
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3e57c35388114772b91916e68ebcfb95
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spelling	oai:doaj.org-article:3e57c35388114772b91916e68ebcfb952021-12-02T15:07:56ZTRPV1 enhances the afferent response to P2X receptor activation in the mouse urinary bladder10.1038/s41598-017-18136-w2045-2322https://doaj.org/article/3e57c35388114772b91916e68ebcfb952018-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-18136-whttps://doaj.org/toc/2045-2322Abstract Both TRPV1 and P2X receptors present on bladder sensory nerve fibres have been implicated in mechanosensation during bladder filling. The aim of this study was to determine possible interactions between these receptors in modulating afferent nerve activity. In wildtype (TRPV1+/+) and TRPV1 knockout (TRPV1−/−) mice, bladder afferent nerve activity, intravesical pressure, and luminal ATP and acetylcholine levels were determined and also intracellular calcium responses of dissociated pelvic DRG neurones and primary mouse urothelial cells (PMUCs). Bladder afferent nerve responses to the purinergic agonist αβMethylene-ATP were depressed in TRPV1−/− mice (p ≤ 0.001) and also in TRPV1+/+ mice treated with the TRPV1-antagonist capsazepine (10 µM; p ≤ 0.001). These effects were independent of changes in bladder compliance or contractility. Responses of DRG neuron to αβMethylene-ATP (30 µM) were unchanged in the TRPV1−/− mice, but the proportion of responsive neurones was reduced (p ≤ 0.01). Although the TRPV1 agonist capsaicin (1 µM) did not evoke intracellular responses in PMUCs from TRPV1+/+ mice, luminal ATP levels were reduced in the TRPV1−/− mice (p ≤ 0.001) compared to wildtype. TRPV1 modulates P2X mediated afferent responses and provides a mechanistic basis for the decrease in sensory symptoms observed following resiniferatoxin and capsaicin treatment for lower urinary tract symptoms.Luke GrundyDonna M. DalyChristopher ChappleDavid GrundyRuss Chess-WilliamsNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-10 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Luke Grundy Donna M. Daly Christopher Chapple David Grundy Russ Chess-Williams TRPV1 enhances the afferent response to P2X receptor activation in the mouse urinary bladder
description	Abstract Both TRPV1 and P2X receptors present on bladder sensory nerve fibres have been implicated in mechanosensation during bladder filling. The aim of this study was to determine possible interactions between these receptors in modulating afferent nerve activity. In wildtype (TRPV1+/+) and TRPV1 knockout (TRPV1−/−) mice, bladder afferent nerve activity, intravesical pressure, and luminal ATP and acetylcholine levels were determined and also intracellular calcium responses of dissociated pelvic DRG neurones and primary mouse urothelial cells (PMUCs). Bladder afferent nerve responses to the purinergic agonist αβMethylene-ATP were depressed in TRPV1−/− mice (p ≤ 0.001) and also in TRPV1+/+ mice treated with the TRPV1-antagonist capsazepine (10 µM; p ≤ 0.001). These effects were independent of changes in bladder compliance or contractility. Responses of DRG neuron to αβMethylene-ATP (30 µM) were unchanged in the TRPV1−/− mice, but the proportion of responsive neurones was reduced (p ≤ 0.01). Although the TRPV1 agonist capsaicin (1 µM) did not evoke intracellular responses in PMUCs from TRPV1+/+ mice, luminal ATP levels were reduced in the TRPV1−/− mice (p ≤ 0.001) compared to wildtype. TRPV1 modulates P2X mediated afferent responses and provides a mechanistic basis for the decrease in sensory symptoms observed following resiniferatoxin and capsaicin treatment for lower urinary tract symptoms.
format	article
author	Luke Grundy Donna M. Daly Christopher Chapple David Grundy Russ Chess-Williams
author_facet	Luke Grundy Donna M. Daly Christopher Chapple David Grundy Russ Chess-Williams
author_sort	Luke Grundy
title	TRPV1 enhances the afferent response to P2X receptor activation in the mouse urinary bladder
title_short	TRPV1 enhances the afferent response to P2X receptor activation in the mouse urinary bladder
title_full	TRPV1 enhances the afferent response to P2X receptor activation in the mouse urinary bladder
title_fullStr	TRPV1 enhances the afferent response to P2X receptor activation in the mouse urinary bladder
title_full_unstemmed	TRPV1 enhances the afferent response to P2X receptor activation in the mouse urinary bladder
title_sort	trpv1 enhances the afferent response to p2x receptor activation in the mouse urinary bladder
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/3e57c35388114772b91916e68ebcfb95
work_keys_str_mv	AT lukegrundy trpv1enhancestheafferentresponsetop2xreceptoractivationinthemouseurinarybladder AT donnamdaly trpv1enhancestheafferentresponsetop2xreceptoractivationinthemouseurinarybladder AT christopherchapple trpv1enhancestheafferentresponsetop2xreceptoractivationinthemouseurinarybladder AT davidgrundy trpv1enhancestheafferentresponsetop2xreceptoractivationinthemouseurinarybladder AT russchesswilliams trpv1enhancestheafferentresponsetop2xreceptoractivationinthemouseurinarybladder
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TRPV1 enhances the afferent response to P2X receptor activation in the mouse urinary bladder

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